Glucagon, an antihypoglycemic agent (an agent that increases serum glucose concentrations), is a hormone synthesized and secreted by the α-2 cells of the pancreatic islets of Langerhans that increases blood glucose by stimulating hepatic glyconeogenesis.
Glucagon is a linear peptide of 29 amino acids, and its administration causes a rapid rise in blood glucose making it suitable to treat severe hypoglycemia.
It is commercially available as a parenteral for injection of recombinant DNA origin (Glucagon Diagnostic Kit®, Lilly; Glucagon Emergency Kit®, Lilly; GlucaGen® Diagnostic Kit, Bedford; and most recently, GlucaGen HypoKit®, Novo Nordisk A/S). Glucagon is primarily used for the emergency treatment of severe hypoglycemia if liver glycogen is available (the hyperglycemic response is diminished in conditions associated with starvation, adrenal insufficiency, emaciated or undernourished patients, or in those with uremia or hepatic disease). It also has utility in the radiographic examination of the gastrointestinal tract (stomach, duodenum, small intestine and colon) where a hypertonic state is advantageous. For this purpose, glucagon appears to be as effective as antimuscarinics and is associated with fewer adverse effects.
Furthermore, there are numerous reports of successful utilization of glucagon as a cardiac stimulant for the management of cardiac manifestations of severe beta-blockade overdosage or calcium channel blocker overdossage. These cardiac manifestations, i.e. bradycardia, hypotension, and myocardial depression, have been successfully reverse in patients unresponsive to atropine, epinephrine, dopamine, dobutamine, inarrinone, and the like.
These and further uses may be found in AHFS Drug Information, ASHP, Bethseda, Md., 2005, which is incorporated here by reference.
Intraoral (including buccal and sublingual) administration offers significant advantages over injectable formulations. Intraoral delivery reduces hepatic and gastrointestinal first-pass metabolism and can minimize food effect. More importantly, glucagon can be delivered to a patient with severe hypoglycemia by the patient or care provider via the oral mucosa and without the need or training in the delivery of injected glucagon formulations. Accordingly, there is a need for glucagon dosage forms that can be intraorally administered.
There is also a need for formulations (including oral and intraoral formulations) that have increased bioavailability.